Robert F. Burrows

Safety of Withholding Heparin in Pregnant Women with a History of Venous Thromboembolism

BACKGROUND Women with a history of venous thromboembolism may be at increased risk for venous thromboembolic events during pregnancy. In these women, the decision to give or withhold heparin in the antepartum period is controversial, because accurate estimates of the frequency of recurrent thromboembolic events if antepartum heparin is withheld are not available. METHODS We prospectively studied 125 pregnant women with a single previous episode of venous thromboembolism. Antepartum heparin was withheld, but anticoagulant therapy was given for four to six weeks post partum. Our primary objective was to determine the rate of antepartum recurrence of venous thromboembolism. Laboratory studies were performed to identify thrombophilia in 95 women. RESULTS Three of the 125 women (2.4 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 0.2 to 6.9 percent). There were no recurrences in the 44 women who had no evidence of thrombophilia and who also had a previous episode of thrombosis that was associated with a temporary risk factor. Among the 51 women with abnormal laboratory results or a previous episode of idiopathic thrombosis, or both, 3 (5.9 percent) had an antepartum recurrence of venous thromboembolism (95 percent confidence interval, 1.2 to 16.2 percent). CONCLUSIONS The risk of recurrent antepartum venous thromboembolism in women with a history of venous thromboembolism is low, and therefore routine antepartum prophylaxis with heparin is not warranted.

Incidentally Detected Thrombocytopenia in Healthy Mothers and Their Infants

The unexpected discovery of thrombocytopenia in an asymptomatic pregnant woman--often considered to be equivalent to the diagnosis of idiopathic thrombocytopenic purpura--leads to a variety of interventions, including delivery by cesarean section. However, the actual risk to mothers and their infants posed by incidentally noted thrombocytopenia is not known. To investigate this issue, we performed a prospective study of a group of normal women who delivered at our medical center and their infants during a period of one year. Of the 2263 women who delivered during the year, 1357 were considered to be normal. One hundred twelve of the women (8.3 percent) had mild thrombocytopenia (range of platelet counts, 97 to 150 x 10(9) per liter). The thrombocytopenia had no discernible clinical effect on the women or their infants. The frequency of thrombocytopenia in babies born to this group of women was not appreciably different from that in babies born to the other normal patients who did not have thrombocytopenia, and none of the infants of women with thrombocytopenia had a platelet count of less than 100 x 10(9) per liter. This study demonstrates that the frequency of mild thrombocytopenia is high in normal pregnant women at term and that the thrombocytopenia appears to have no adverse effect on either the mothers or their infants. To perform obstetrical interventions such as cesarean section because of thrombocytopenia in these mothers is not justified.

Pregnancy in patients with idiopathic thrombocytopenic purpura: assessing the risks for the infant at delivery.

The objective of this review is to estimate the risk of severe thrombocytopenia at birth and minor or major morbidity for the infant of a pregnancy complicated by immune thrombocytopenic purpura. English language publications on immune thrombocytopenic purpura in pregnancy from January 1980 to December 1990 were used. Manuscripts considered for infant risk assessment fulfilled the following criteria: 10 or more entrants, reported fetal platelet samples (cordocentesis, scalp sampling or cord sample at birth), and provided all infant platelet data. All other data not fulfilling these criteria are reported. The main results were 11 manuscripts reporting 288 live-born infants fulfilled the criteria enabling assessment of infant risk. There were no deaths or intracranial hemorrhages in these studies and secondary morbidity occurred in 3.5 per cent (95 per cent Cl 1.4–5.6 per cent). An infant platelet count of less than 50 × 109 per liter was reported in 10.1 per cent (95 per cent Cl 6.6–13.6 per cent) and an infant platelet count of less than 20 × 109 per liter occurred in 4.2 per cent (95 per cent Cl 1.9–6.5 per cent). Neither cordocentesis, scalp sample, nor umbilical cord sampling at birth altered the outcome of these infants and minor morbidity occurred equally in vaginal and cesarean births. Smaller case reports (less than 10 entrants) significantly over-estimated the prevalence of severe infant thrombocytopenia and secondary morbidity. All deaths and intracranial hemorrhages were reported in manuscripts which did not specify the timing of infant platelet count determination; thus the relationship of these events to the event of birthing was unclear. In conclusion, this review indicates that the infant risk in an immune thrombocytopenic purpura pregnancy is much lower than previously thought. Aggressive investigations or interventions in pregnant immune thrombocytopenic purpura patients are not supported by this analysis of the literature.

Low fetal risks in pregnancies associated with idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura and pregnancy are commonly associated. In this article we describe our experience in the management of 61 infants born to 50 mothers with confirmed idiopathic thrombocytopenic purpura. The focus was the neonatal cord platelet count, the parameter of greatest interest to obstetricians. None of the 61 infants had morbidity or mortality as a consequence of the thrombocytopenia. Only three of 61 infants (4.9%) had a cord platelet count that was less than 50 x 10(9) per liter. Although 66% of the infants had a further fall in the platelet count after birth, in all the thrombocytopenia could readily be corrected. Neither maternal platelet count, maternal treatment with corticosteroids, maternal platelet-associated immunoglobulin G level, nor maternal splenectomy could be used to predict neonatal thrombocytopenia. Fetal scalp platelet sampling was likely to lead to an erroneous decision. The rareness of a poor neonatal outcome raises the question of whether obstetric interventions are justified for every pregnant patient with idiopathic thrombocytopenic purpura.

Bleeding risk and reproductive capacity among patients with factor XIII deficiency: a case presentation and review of the literature.

Factor XIII deficiency is an uncommon, inherited bleeding disorder that usually manifests in infancy or early childhood, involving both boys and girls. We present the case of a woman who had experienced two previous intracranial bleeding events, and was treated before and during her current pregnancy with factor XIII concentrate. Her pregnancy was successful, and she experienced an uncomplicated vaginal delivery. To better understand the issues surrounding bleeding, reproductive capacity, and management of factor XIII deficiency during pregnancy, we conducted a systematic literature review using MEDLINE from 1966 to December 1998. We also examined the bibliographic references from all articles, and included all cases, case reports, or case series of patients with factor XIII deficiency. We retrieved data on 117 patients from 37 articles, the majority of which had type II deficiency. Among untreated patients with type II factor XIII deficiency, the literature suggests an elevated mortality rate due to uncontrolled bleeding and intracranial hemorrhage. Because of its high degree of efficacy, the evidence supports the use of life long prophylactic therapy with at least monthly infusions of factor XIII concentrate, including during pregnancy. The opinion that women with type II factor XIII deficiency have inevitable recurrent abortions, or that men are sterile, is not well substantiated. No data were found on whether treatment alters male reproductive capacity. A policy of universal factor XIII replacement, starting in childhood, will likely enable more patients to attain reproductive status. The development of an international data registry would optimally address both bleeding risk and reproductive capacity among patients with factor XIII deficiency.

The feasibility of a control population for a randomized control trial of seizure prophylaxis in the hypertensive disorders of pregnancy

OBJECTIVE To document the feasibility of a control population for a randomized controlled trial, we report our experience in managing hypertensive pregnancies without seizure prophylaxis. STUDY DESIGN An 8-year cross-sectional study in one institution was performed of all hypertensive patients. RESULTS Of 467 patients with preeclampsia or superimposed preeclampsia managed without seizure prophylaxis, 18 had seizure activity, 3.9% (95% confidence interval 2.3% to 6.0%). There was no seizure-related maternal mortality or major morbidity, and the perinatal mortality rate after 28 gestational weeks was the same in patients with or without seizures. By logistic regression seizures were 17.4 times more likely in preeclampsia and 8.1 times more likely in chronic hypertension with superimposed preeclampsia, compared with gestational or chronic hypertension alone. CONCLUSION The rate of seizures in patients with preeclampsia or superimposed preeclampsia managed without seizure prophylaxis was low and unassociated with an increase in maternal or perinatal mortality. A control arm is feasible in a randomized, controlled trial to address the issue of whether antiseizure medication can prevent eclampsia.

Platelet specific alloantigens on the platelet glycoprotein Ia/IIa complex

Summary The majority of platelet alloantigens are located on platelet glycoproteins IIb/IIIa. This report describes a codominant allelic system carried on the glycoprotein la/IIa complex, which we originally designated as Zava/Zavb but which is identical to the Bra/Brb system. Furthermore Zava was found to be identical to Hca. The alloantigens could not be detected using a direct binding enzyme immunoassay (EIA) with intact platelets, but were readily detected using a glycoprotein capture EIA and by radioimmunoprecipitation techniques. The two index cases (designated as homozygous Zava and Zavb) had alloantibodies against the corresponding antigen and did not react with their own platelets. Using these alloantibodies and a monoclonal antibody that reacts with the platelet glycoprotein la/IIa complex (12F1). We demonstrated that all Ia/IIa molecules carry either Zava or Zavb and we found that Zava and Zavb are on discrete populations of Ia/IIa. Following immunodepletion using either anti‐Zava or anti‐Zavb, all detectable Ia/IIa complexes from the respective homozygous platelets were removed. Immunodepletion of heterozygous Zava/Zavb with either anti‐Zava or anti‐Zavb did not reduce the amount of Ia/IIa complexes precipitable using the alternate alloantiserum. Population studies (n= 50) indicated the phenotypic frequency of Zava/Zava is less than 1%; Zava/Zavb is 18% and Zavb/Zavb is 82%. Four different alloantisera that had either anti‐Zava or anti‐Zavb reactivity also carried reactivity against the Baka or Bakb antigens which may suggest an association in the immune response to these alleles.

False diagnosis of intestinal obstruction in a fetus with congenital chloride diarrhea

Intestinal obstruction is often diagnosed prenatally by ultrasound, providing an opportunity for prenatal counseling, genetic investigation, and planned delivery at a perinatal center. We describe a patient with typical features of fetal bowel obstruction, who was found at birth to have congenital chloride diarrhea. A 25-year-old white woman had marked polyhydramnios; multiple dilated, fluid-filled loops of intestine were seen in the fetal abdomen on prenatal ultrasound. However, postnatally, there was no evidence of bowel obstruction. The infant girl passed large amounts of watery stools, but tolerated feeds well. A rectal biopsy showed normal ganglion cells. On the fourth day of life her serum sodium and chloride were markedly decreased, and stool chloride levels were diagnostic of congenital chloride diarrhea. She was placed on sodium chloride and potassium chloride supplements, and her serum electrolytes normalized. Congenital chloride diarrhea is a rare, inherited condition caused by an abnormality of intestinal electrolyte transport. This case illustrates that it may present prenatally with a picture similar to that seen with intestinal obstruction.

Cesarean Section: Analysis of the Experience Before and After The National Consensus Conference on Aspects of Cesarean Birth

OBJECTIVE To examine the effect of recommendations to reduce the cesarean section rate issued by the National Consensus Conference on Aspects of Cesarean Birth in 1986 on obstetric practices and to identify current patient factors that predict cesarean section. DESIGN Descriptive retrospective cross-sectional study. SETTING A tertiary care perinatal referral centre and a general teaching hospital with a level 2 nursery in Hamilton, Ont. PATIENTS All patients who gave birth at the two hospitals in 1982 (4121 women) and 1990 (4431). MAIN OUTCOME MEASURES Cesarean section rates and indications and predictors of cesarean section. RESULTS Although a trial of vaginal delivery after cesarean section was offered 93% more often in 1990 than in 1982 (p = 0.0002), the rate of vaginal delivery increased only 2.6%, for a reduction of 8.7% in the total cesarean section rate and of 15% in the repeat cesarean section rate. The incidence rate and treatment of dystocia did not change. The rate of cesarean section for breech presentation remained unchanged, and fetal distress was rarely confirmed with pH measurement in scalp blood before cesarean section. The most important predictors of cesarean section in 1990 were previous cesarean section and labour induction. For the nulliparous women and the multiparous women with no previous cesarean section labour induction was the most important predictor. CONCLUSIONS The rate at which patients with previous cesarean section are offered a trial of vaginal delivery has increased significantly since 1982; however, the total and repeat cesarean section rates have not decreased proportionally. Induction of labour is currently the most important correctable predictor of cesarean section. The active management of dystocia, efforts to increase the rate of vaginal breech delivery and appropriate methods to diagnose fetal distress need to be improved; such improvements should reduce the cesarean section rate further.

Thrombocytopenia at delivery: A prospective survey of 6715 deliveries

infection than in controls (1,2%) (p < 0.001, 0.01 respectively). Symptomatic infections were seen only among women with a history of urinary infection: four women with renal scarring (three of whom had vesico ureteric reflux) developed pyelonephritis and three cystitis, and one woman without scarring developed pyelonephritis. Mean blood pressure was higher among women with severe renal scarring than controls (4/l 1 v 3/44; p < 0.05) before and during pregnancy. There was no significant difference in the incidence of preeclampsia, operative delivery, prematurity, or birth weight. Conclusions Women with a history of previous urinary infections had a high incidence of bacteriuria during pregnancy, and those with renal scarring and presistent reflux were prone to develop acute pyelonephritis. The risk of serious complications in pregnancy, however, was not increased in women with severe reneal scaring, possibly owing to their continuous clinical supervision.